Journal
ORAL DISEASES
Volume 24, Issue 4, Pages 580-590Publisher
WILEY
DOI: 10.1111/odi.12813
Keywords
biomarkers; chronic graft-versus-host disease; oral mucosa; topical therapy
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Funding
- Dana-Farber Cancer Institute Ted and Eileen Pasquarello Research Fund [5 P01-CA142106-07, R01-CA183559]
- Brazilian program Science Without Borders [5 P01-CA142106-07, R01-CA183559]
- NATIONAL CANCER INSTITUTE [P01CA142106, R01CA183559] Funding Source: NIH RePORTER
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ObjectiveTo characterize the immunohistopathological features of oral chronic graft-versus-host disease (cGVHD), and the impact of topical immunomodulatory therapy on the infiltrating cells. Material and MethodsPaired oral cGVHD biopsies obtained before (n=12) and 1month after treatment (n=12) with topical dexamethasone (n=8) or tacrolimus (n=4) were characterized by immunohistochemistry using a panel of CD1a, CD3, CD4, CD8, CD20, CD31, CD62E, CD103, CD163, c-kit, and FoxP3. Controls included acute GVHD (aGVHD; n=3), oral lichen planus (OLP; n=5), and normal tissues (n=5). ResultsOral cGVHD specimens prior to treatment were mainly characterized by basal cell squamatization, lichenoid inflammation, sclerosis, apoptosis, and lymphocytic exocytosis. The infiltrating cells in oral cGVHD primarily consisted of CD3(+), CD4(+), CD8(+), CD103(+), CD163(+), and FoxP3(+) cells, which were higher than in normal tissues. Topical dexamethasone or tacrolimus reduced neutrophilic exocytosis, basal cell squamatization, and lichenoid inflammation in oral cGVHD, and dexamethasone reduced the number of CD4(+) and CD103(+) cells. ConclusionThe high expression of CD3, CD4, CD8, CD103, CD163, and FoxP3 confirms that oral cGVHD is largely T-cell-driven with macrophage participation. The impact of topical immunomodulatory therapy was variable, reducing histological inflammatory features, but with a weak clinicopathological correlation. Topical dexamethasone reduced the expression of CD4 and CD103, which may offer novel therapeutic targets.
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